Roles of Pro- and Anti-Inflammatory Cytokines in the Pathogenesis of SLE

Su, Dinglei; Lu, Zhimin; Shen, Minning; Li, Xia; Sun, Lingyun

doi:10.1155/2012/347141

Cited by 156 publications

(141 citation statements)

References 166 publications

(177 reference statements)

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…We first investigated whether GARP is aberrantly expressed on immune cells in the lupus-prone NZM2410 mouse model. Similar to human studies, prior experiments in lupus-prone mice have demonstrated reduced TGF-β levels, predisposing the system to immune dysregulation and autoantibody production (54,55). We found that GARP was significantly elevated on CD19 + B cells in the splenic compartment of 24-week-old NZM2410 mice with lupus but not young healthy mice (Supplemental Figure 2A).…”

Section: Bm Chimera Garp-ko Mice Have Increased Susceptibility To Chesupporting

confidence: 85%

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex

Wallace¹,

Wu²,

Salem³

et al. 2018

JCI Insight

View full text Add to dashboard Cite

Section: Bm Chimera Garp-ko Mice Have Increased Susceptibility To Chesupporting

confidence: 85%

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex

Wallace¹,

Wu²,

Salem³

et al. 2018

JCI Insight

View full text Add to dashboard Cite

“…2 D). There is evidence that IL-6, IL-10, IL-17A, IL-17F, TNF-α, and IFNs markedly contribute to the immune imbalance in SLE [21][22][23][24]. To further investigate the impact of TLR2 stimulation on the inflammatory response of CD4 + T cells from SLE patients, we collected the supernatant of cell culture in vitro and performed ELISA to detect the concentration of proinflammatory cytokines secreted by CD4 + T cells from SLE patients after TLR2 stimulation.…”

Section: Tlr2 Stimulation Aggravates the Inflammatory Response Of Cd4mentioning

confidence: 99%

Increased expression of TLR2 in CD4⁺ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications

et al. 2015

View full text Add to dashboard Cite

The innate immune system has been shown to play an important pathologic role in systemic lupus erythematosus (SLE). TLR2, a PRR, recognizes exogenous PAMPs, and endogenous damage-associated molecular patterns and has been implicated in the initiation and maintenance of the perpetuated inflammatory reactions in autoimmune diseases. Here, we report increased expression of TLR2 in CD4+ and CD8 + T cells, CD19 + B cells, and CD14 + monocytes from SLE patients. Conventional treatment, such as hydroxychloroquine and corticosteroids, showed no effect on TLR2 expression in CD4 + T cells from SLE patients. In vitro stimulation of TLR2 in CD4 + T cells from SLE patients increased CD40L and CD70 expression, as well as secretion of IL-6, IL-17A, IL-17F, and TNF-α, while Foxp3 transcription decreased. This effect was reversed by TLR2 siRNA. Moreover, TLR2 activation upregulated H3K4 tri-methylation and H4 acetylation levels while downregulated H3K9 tri-methylation level in the IL-17A promoter region. In addition, it also increased H4 acetylation levels and decreased H3K9 tri-methylation levels in the IL-17F promoter region. In summary, our findings demonstrate that increased expression of TLR2 contributes to immune reactivity and promotes IL-17A and IL-17F expression through histone modifications in SLE.Keywords: Histone modification r IL-17 r Systemic lupus erythematosus r T cells r TLR2 IntroductionSystemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease that results in multiple organ damage and diverse clinical manifestations [1]. SLE is characterized by T-cell hyperactivity and B-cell overstimulation. Uncontrolled T-cell activation results in increased secretion of inflammatory cytokines, production of autoantibodies, and aberrant inflamCorrespondence: Prof. Qianjin Lu e-mail: qianlu5860@gmail.com matory response, which contribute to the development of SLE [2]. How T cells become hyperactive during SLE remains to be determined. However, both genetic background and environmental factors are believed to contribute to the development of SLE [3]. A number of epidemiological studies have suggested that onset and flares of SLE are associated with infection [4]. One of the mechanisms whereby invasive microorganisms disrupt host immune system is through the interaction with TLRs, as demonstrated in experimental lupus [5,6]. * These authors contributed equally to this work. Eur. J. Immunol. 2015. 45: 2683-2693 TLRs are membrane-bound proteins referred to as pathogenassociated molecular patterns that belong to innate immune system. Each TLR can recognize a specific set of microbes bearing PAMPs and endogenous damage-associated molecular patterns (DAMPs) [7]. Activation of TLRs can trigger intracellularsignaling cascades and upregulate the expression of inflammatory cytokines [8]. TLR2 is a cell-surface TLR with extracellular recognition domain that can bind with exogenous ligands including lipoproteins, peptidoglycan, lipoteichoic acid, and endogenous DAMPs, such as HSP70 and high mobility group box protei...

show abstract

“…Interleukin 17A is a multifunctional cytokine that impacts neutrophil recruitment, mediating both T-helper-1 (Th1) and T-helper-2 (Th2) cytokine production, and it possesses angiogenic properties through apoptosis modulation (3,12,13). IL-17A production, in vivo and in vitro, is primarily controlled by transforming growth factor beta 1 (TGF-β1) and interleukin 6 (IL-6) via the activation of signal transducer and activator of transcription 3 (STAT-3) in mouse and human models, respectively (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role

Raymond¹,

Ostli-Eilertsen²,

Griffiths³

et al. 2017

Eur J Rheumatol

View full text Add to dashboard Cite

Objective: The interleukin 17 (IL-17) cytokine family is involved in a number of chronic inflammatory diseases. In spite of contradictory findings and a lack of causality in clinical studies, IL-17 inhibition for systemic lupus erythematosus (SLE) has regained attention as a potential therapeutic pathway, after demonstrating disease-modifying capabilities in ankylosing spondylitis. We investigated the clinical associations of interleukin 17 A (IL-17A) in patients with SLE.Material and Methods: A cross-sectional study was performed involving SLE patients (n=102; age: 49 years; 86% female) recruited from a regional registry. IL-17A levels were determined by immunoassay, disease activity by Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K), and cumulative damage by Systemic Lupus International Collaborative Clinics Damage Index (SDI) scores. Non-parametric techniques were used to examine the association between IL-17A and disease activity and autoantibody profiles were compared with healthy controls (n=31): principal component analysis (PCA) was used to determine the interplay of immune cells across disease states and damage development in SLE patients.Results: SLE patients had higher IgG levels, lower T-cell and B-cell counts, but median IL-17A levels did not differ from the controls (28.4 vs. 28.4 pg/mL, p=0.9). In SLE patients, IL-17A did not correlate with SLEDAI-2K or SDI, but was inversely related with age (correlation coefficients, Rs.=-0.29, p<0.05), systolic blood pressure (Rs.=-0.31, p<0.05), years of smoking (Rs.=-0.43, p<0.05), cumulative heart (Rs.=-0.22, p<0.05), and malignancy damage (Rs.=-0.18, p<0.05). Serological correlations for IL-17A existed with immunoglobulin G (IgG) levels (Rs.=0.21, p<0.05), high sensitivity C-reactive protein (hs-CRP) levels (Rs.=0.28, p<0.05), proteinuria (Rs.=0.64, p<0.05), and pre-albumin (Rs.=-0.22, p<0.05). Longitudinal data showed only modest fluctuation in IL-17A levels, independent of SLEDAI-2K. Conclusion:These results suggest that IL-17A, while participating in inflammation, may also serve a protective purpose in SLE patients.

show abstract

Roles of Pro- and Anti-Inflammatory Cytokines in the Pathogenesis of SLE

Cited by 156 publications

References 166 publications

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex

Increased expression of TLR2 in CD4⁺ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications

IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role

Contact Info

Product

Resources

About

Roles of Pro- and Anti-Inflammatory Cytokines in the Pathogenesis of SLE

Cited by 156 publications

References 166 publications

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex

Increased expression of TLR2 in CD4+ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications

IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role

Contact Info

Product

Resources

About

Increased expression of TLR2 in CD4⁺ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications